Immunolocalization of tumor necrosis factor‐α expressing cells in recurrent aphthous ulcer lesions (RAU)

Abstract

Tumor necrosis factor (TNF)-alpha is a pro-inflammatory cytokine and crucial mediator in many aspects of immunity. Although several studies have shown that recurrent aphthous ulcers (RAU) can be prevented by treatment that prevents the synthesis of endogenous TNF-alpha little is known about the location and distribution of TNF-alpha-expressing cells at disease sites. The aim of the present work is, therefore, to investigate TNF-alpha and its cellular distribution in RAU lesions compared with those in induced oral traumatic ulcers (TUs). Twelve biopsies of RAU lesions of oral mucosa were obtained from 12 patients with RAU. They were compared to a control group consisting of ten samples of induced TUs. All samples were analyzed for TNF-alpha expression by using monoclonal mouse anti-human TNF-alpha antibody in avidin-biotin-peroxidase complex (ABC) staining. Results were quantified by a semi-automatic VIDAS image analysis system. TNF-alpha immunoreactivity was contained mainly in monocyte/macrophages and lymphocytes within the mononuclear inflammatory infiltrates. TNF-alpha was often seen in mast cells and vascular endothelial cells in connective tissue lateral to the inflammatory infiltrates. Interestingly, 32%-60% of the mononuclear cells were found to be TNF-alpha immunoreactive in RAU lesions. TNF-alpha containing cells were more numerous in aphthae (188+/-46 cells/0.2 mm2) compared with controls (52+/-14 cells/0.2 mm2, P<0.001). These findings suggest that RAU lesions are characterized by high expression of TNF-alpha. Because such expression occurred in the mononuclear inflammatory cells, mast cells and vascular endothelial cells, TNF-alpha, which is a major inflammatory mediator, may contribute to the activation and recruitment of leukocytes that are found in RAU lesions.

IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS)

“…6 These changes are consistent with release of pro-inflammatory cytokines such as IL-1, IL-6, TNF and interferon-␥. [6][7][8] Indeed, elevated levels of TNF␣, interferon-␥, IL-2, IL-4 and IL-5 have been detected in ulcer tissue 7,8 and raised levels of IL-6 in the circulation. 9 It has been suggested that RAS is precipitated by local trauma in an individual genetically predisposed to an exaggerated or abnormal cytokine cascade.…”

A Case of Refractory Oral Aphthous Ulcer Successfully Treated with Adalimumab

“…One study reported that oral ulcer is characterized by high expression of TNF-α. This major inflammatory mediator may contribute to the activation and recruitment of leukocytes that are found in oral ulcers [6]. There are currently 5 TNF-α inhibitors approved in rheumatic diseases which are divided two strategies: soluble receptors (etanercept) and targeting monoclonal antibodies (infliximab, adalimumab, golimumab, certolizumab).…”

Tratamento da estomatite aftosa recorrente: uma revisão integrativa da literatura

“…Adicionalmente, estudos patológicos de úlceras aftosas têm revelado que o TNF-α está presente principalmente em macrófagos/monócitos e linfócitos contidos no infiltrado inflamatório mononuclear que está presente nessas lesões 9 . Três subtipos clínicos da EAR têm sido estabelecidos de acordo com seu tamanho, número, duração e agudizações: EAR menor, EAR maior, EAR herpetiforme.…”